Interactions between viruses and the host immune system have been long associated with the occurrence of autoimmune phenomena and lymphoproliferative disorders in experimental animals and may be causally related to similar phenomena in humans. We are studying a model of type-C retrovirus induced auto/allo-aggression by murine lymphocytes that appears to be associated with lymphomagenesis in C3H/He and BALB/c mice. These animals, persistently infected with infectious Moloney murine leukemia virus since birth (MuLV-M-carriers), have thymocytes that kill normal syngeneic and some allogeneic target cells, but spare normal xenogeneic or MuLV-infected target cells as determined by an in vitro microcytotoxicity assay. Many, but not all, thymic lymphomas arising in these mice behave similarly when they are used as effector cells. Cloning experiments indicate that these T cells lymphomas are phenotypically heterogenous. Major objectives of our studies presently include: (1) characterizing differences among the lymphoma isolates and their clones in terms of their T cell markers, possible functional expressions, MuLV expression and production, and their immunogenicity, etc.; (2) defining the relationship between these lymphomas and the aggressor thymocytes we see in preleukemic MuLV-M-carriers; (3) defining the mechanism of target cell kill by MuLV-M-carrier thymocytes as well as the mechanism of sparing of MuLV-infected target cells; (4) determining whether the phenomena we see in MuLV-M-carrier mice also occur in strains of mice that normally have high incidence of spontaneous lymphoma (e.g., AKR and homozygous recessive (hr/hr) HRS/J mice).